Gel material for regenerative medicine

Abstract

An object of the present invention is to provide a novel use in which a polymer gel material having a µm-scale porous structure can be suitably used. A gel material for regenerative medicine comprising a polymer gel in which hydrophilic polymer units are crosslinked with each other, wherein the polymer gel contains water as a solvent and has a three-dimensional network structure having two regions: a first region in which the polymer units are densely present and a second region in which the polymer units are sparsely present, and a mesh size composed of the first region is the range of 1 to 500 µm.

1 . A gel material for regenerative medicine comprising a polymer gel in which hydrophilic polymer units are crosslinked with each other,
 wherein the polymer gel contains water as a solvent and has a three-dimensional network structure having two regions: a first region in which the polymer units are densely present and a second region in which the polymer units are sparsely present, and a mesh size composed of the first region is the range of 1 to 500 µm.   
     
     
         2 . The gel material for regenerative medicine according to  claim 1 , wherein the gel material has a lower transmittance than a transmittance of the polymer units before gelation. 
     
     
         3 . The gel material for regenerative medicine according to  claim 1  or  2 , wherein the gel material has an osmotic pressure of ⅕ to ½ of an osmotic pressure of the polymer units before gelation. 
     
     
         4 . The gel material for regenerative medicine according to any one of  claims 1 to 3 , wherein an osmotic pressure (Π os ) and an elastic pressure (Π el ) after a lapse of a certain period of time from gelation have a relationship of Π el  > Π os . 
     
     
         5 . The gel material for regenerative medicine according to any one of  claims 1 to 4 , wherein a polymer concentration in the first region is from 10 to 99 wt%, and a polymer concentration in the second region is from 0 to 1 wt%. 
     
     
         6 . The gel material for regenerative medicine according to any one of  claims 1 to 5 , wherein the polymer gel has a polymer content of 5 wt% or less. 
     
     
         7 . The gel material for regenerative medicine according to any one of  claims 1 to 6 , wherein the polymer units are polymers having a polyethylene glycol backbone or a polyvinyl backbone. 
     
     
         8 . The gel material for regenerative medicine according to any one of  claims 1 to 7 , wherein the polymer units comprise a first polymer unit having one or more nucleophilic functional groups in a side chain or at an end and a second polymer unit having one or more electrophilic functional groups in a side chain or at an end. 
     
     
         9 . The gel material for regenerative medicine according to  claim 8 , wherein the nucleophilic functional groups are selected from the group consisting of a thiol group and an amino group, and the electrophilic functional groups are selected from the group consisting of a maleimidyl group, an N-hydroxy-succinimidyl (NHS) group, a sulfosuccinimidyl group, a phthalimidyl group, an imidazolyl group, an acryloyl group, a nitrophenyl group, and —CO 2 PhNO 2 . 
     
     
         10 . The gel material for regenerative medicine according to any one of  claims 1 to 9 , which is used for regeneration of a tissue. 
     
     
         11 . The gel material for regenerative medicine according to  claim 10 , wherein the tissue is bone, cartilage, skin, or nerve. 
     
     
         12 . A treatment process using the gel material for regenerative medicine according to any one of  claims 1 to 11 . 
     
     
         13 . A kit for producing a gel material for regenerative medicine, the kit comprising the following two types of solutions (A) and (B) stored without being mixed with each other:
 (A) an aqueous solution containing a hydrophilic first raw polymer having a concentration of less than an overlapping concentration and equal to or more than a critical gelation concentration; and   (B) an aqueous solution containing a hydrophilic second raw polymer having a concentration of less than an overlapping concentration and equal to or more than a critical gelation concentration;   wherein the solution (A) and/or the solution (B)further contains a non-reactive polymer having no functional group capable of crosslinking with the raw polymer in the molecule,   a polymer gel obtained by mixing the solutions (A) and (B) is a polymer gel in which the first raw polymer and the second raw polymer are crosslinked with each other, and   the polymer gel has a structure including two regions: a first region in which polymer units derived from the raw polymers are densely present and a second region in which polymer units derived from the raw polymers are sparsely present.   
     
     
         14 . A kit for producing a gel material for regenerative medicine, the kit comprising the following two types of solutions (A′) and (B′) stored without being mixed with each other:
 (A′) an aqueous solution containing a first gel precursor, wherein the first gel precursor is obtained by crosslinking hydrophilic raw polymers under conditions of less than an overlapping concentration and less than a critical gelation concentration, and the first gel precursor has a relationship of G′ < G″ between a storage modulus G′ and a loss modulus G″; and 
 (B′) an aqueous solution containing a second gel precursor, wherein the second gel precursor is obtained by crosslinking hydrophilic raw polymers under conditions of less than an overlapping concentration and less than a critical gelation concentration, and the second gel precursor has a relationship of G′ < G″ between a storage modulus G′ and a loss modulus G″; 
 wherein the solution (A′) and/or the solution (B′)further contains a crosslinking agent, 
 a polymer gel obtained by mixing the solutions (A′) and (B′) is a polymer gel in which the first raw polymer and the second raw polymer are crosslinked with each other, and 
 the polymer gel has a structure including two regions: a first region in which polymer units derived from the raw polymers are densely present and a second region in which polymer units derived from the raw polymers are sparsely present. 
 
     
     
         15 . The kit according to  claim 13  or  14 , wherein the raw polymers are polymers having a polyethylene glycol backbone or a polyvinyl backbone. 
     
     
         16 . The kit according to any one of  claims 13 to 15 , wherein the raw polymers comprise a first polymer having one or more nucleophilic functional groups in a side chain or at an end and a second polymer having one or more electrophilic functional groups in a side chain or at an end. 
     
     
         17 . The kit according to  claim 16 , wherein the nucleophilic functional groups are selected from the group consisting of a thiol group and an amino group, and the electrophilic functional groups are selected from the group consisting of a maleimidyl group, an N-hydroxy-succinimidyl (NHS) group, a sulfosuccinimidyl group, a phthalimidyl group, an imidazolyl group, an acryloyl group, a nitrophenyl group, and —CO 2 PhNO 2 . 
     
     
         18 . The kit according to  claim 13 , wherein the non-reactive polymer is polyethylene glycol or cellulose, which has no crosslinking reactive group. 
     
     
         19 . The kit according to  claim 14 , wherein the first gel precursor and the second gel precursor both have a first polymer having one or more nucleophilic functional groups in a side chain or at an end and a second polymer having one or more electrophilic functional groups in a side chain or at an end, the first gel precursor has a higher first polymer content than a second polymer content, and the second gel precursor has a higher second polymer content than a first polymer content. 
     
     
         20 . The kit according to  claim 14 , wherein the gel precursors have a diameter of 10 to 1000 nm. 
     
     
         21 . A process for producing a gel material for regenerative medicine in vivo using the kit according to any one of  claims 13 to 20 . 
     
     
         22 . Use of the kit according to any one of  claims 13 to 20  in tissue regeneration treatment.